Propafenone

Propafenone. Propafenone hydrochloride, an arylketone, is stmcturaHy similar to the P-adrenoceptor blocking agents. It has been in use in the former West Germany since 1977 and was introduced in the United States in 1990. Its effects may result from a combination of weak calcium channel blocking, weak nonselective -adrenoceptor blocking, and sodium channel blocking activity. Propafenone is effective in treating supraventricular tachyarrhythmias, ventricular ectopic beats, and ventricular arrhythmias. It is the most frequendy prescribed medication for ventricular arrhythmias in Europe (32). 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Patients taking propafenone may experience a metallic taste after ingesting the dmg (32). 

Endomethylene-A -tetrahydro benzaldehyde Cyclothiazide Epibromohydrin Carteolol Epichlorohydrin Acebutolol Atenolol Befunolol Betaxolol HCI Bufetrol Bunitrolol Bupranolol Carazolol Carnitine Celiprolol Colestipol Cromolyn sodium I ndenolol Mazindol Mepindolol Metoprolol tartrate Nadolol Nifuratel Oxprenolol Penbutolol Practolol Propafenone HCI Propranolol HCI Viloxazine HCI Xanthinol niacinate Epinephrine... 

Ryegonovin - Methylergonovine maleete Rynecrom - Cromolyn sodium Rythmical - Disopyramide phosphate Rythmoden - Disopyramide phosphate Rythmodul Disopyramide phosphate Rytmil - Bisacodyl Rytmilen - Disopyramide phosphate Rytmonorm - Propafenone HCI... 

I c With only little effect on action potential duration Lorcainide, Flecainide, Propafenone... 

Class IC antiarrhythmic drugs such as flecainide or propafenone block the Na+ channel (open state propafenone open and inactivated state) with a very long dissociation time constant so that they alter normal action potential propagation. Flecainide increased mortality of patients recovering from myocardial infarction due to its proarrhythmic effects (CAST study). Action potential is shortened in Purkinje fibres but is prolonged in the ventricles. 

Propafenone possesses (3-adrenoceptor antagonistic effects due to its structural similarity to propranolol. 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

Flecainide (Tambocor) and propafenone (Rythmol) are examples of class I-C drags. These drugs have a direct stabilizing action on the myocardium, decreasing the height and rate of rise of cardiac action potentials, thus slowing conduction in all parts of the heart. 

Propafenone is administered orally every 8 hours. Any previously given antiarrhythmic drug should be discontinued before propafenone therapy is started. Dosage changes are done 3 to 4 days apart because of the length of time the drug remains active in the body. 

ADMINISTERING FLECAINIDE AND PROPAFENONE. When administering flecainide, die nurse must carefully monitor die patient for cardiac arrhythmias. Therapeutic serum levels fall between 0.2 and 1 pg/mL. Life support equipment, including pacemaker, should be kept on stand-by during administration. 

During die initiation of therapy, patients taking propafenone must be monitored carefully. To minimize adverse reactions, dosage is increased slowly at a minimum of 3- to 4-day intervals. Periodic ECG monitoringis necessary to evaluate the effects on cardiac conduction. 

CyHyNO 21850-61-3) see Benoxaprofen Flunoxaprofen 2 -hydroxy-3-phenylpropiophenone (C15H14O2 3516-95-8) see Etafenone Propafenone (2S-cw)-4-hydroxy-4-phenyI-l,2-pyrroIidinedicarboxyIic acid l-(phenylmethyl) ester (CiyHiyN05 78464-03-6) see Fosinopril a hydroxy-a-phenyl-2-thiopheneacetic acid 2-diethylami-noethyl ester... 

I- [2-(oxiranylmethoxy)phenyl]-3-phenyl-l-propanone (CijHijOj 22525-95-7) see Propafenone... 

C Hi N I07-W-H) see Carticaine Cropropamide Etidocaine Prilocaine Propafenone propyl benzenesulfonate (CjHijOjS KO-42-2) see Propoxycaine propyl bromide... 

Albumin, aminophylline, aspirin, heparin, insulin, metoclopramide, NSAIDs, muromonab-CD3 (OKT3), opiates, penicillins, propafenone, quinidine, senna, sulfonamide antimicrobials, and vancomycin... 

Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Clofibrate Danazol Disulfiram Doxycycline Erythromycin Fenofibrate Fluconazole Fluorouracil Fluoxetine Fluvoxamine Gemfibrozil Influenza vaccine Isoniazid Itraconazole Fovastatin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone Piroxicam Propafenone Propoyxphene Quinidine Sertraline Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Vitamin E Zafirlukast... 

Schmid, D., Ecker, G., Kopp, S., Hitzler, M., Chiba, P., Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements, Biochem. Pharmacol. 1999, 58, 1447-1456. 

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